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Exploring neurological & mental brain disorders in Europe
Stephanie Kramer and Frédéric Destrebecq of the European Brain Council discuss updates on Brain disorders in Europe – neurological and mental alike. Brain disorders are widespread in Europe, highly disabling and often difficult to treat. Approximately 60% of the European population lives with a neurological condition, and one in six citizens in Europe is affected by mental ill-health. To Kramer and Destrebecq, investing in the brain and brain research is critical. However, instead of divesting in a cost, policymakers and society at large should view the prioritisation and support of research into brain disorders as an investment into a healthier future. Calling for prioritisation of research of brain disorders at the political level has been a major effort from the brain research community for decades, but, despite a steady growth of investment by the European Union, it has been nowhere near enough, lacks efficiency, remains fragmented, lacks recognition as a priority area, and is persistently misunderstood and underestimated.

Brain disorders pose major challenges to medicine and treatment innovation. This is because their spectrum spans inflammatory, degenerative, traumatic/ischaemic, and neoplastic disease processes with a complex and often ill- understood aetiology. An improved genetic and genomic understanding of specific disease pathways offers new approaches to these challenges, but at present it is in its infancy. Here, we review different aspects of the challenges facing neuromedicine, give examples of where there are advances, and highlight challenges to be overcome. We see that some disorders such as Huntington's disease are the product of single gene mutations, whose discovery has been leading to the development of new targeted interventions. In the field of neurosurgery, the identification of a number of mutations allows an elaborated genetic analysis of brain tumours and opens the door to individualised therapies. Psychiatric disorders remain the area where progress is slow. Genetic analyses show that for major common disorders such as schizophrenia and depression there are no single gene alterations which offer options for targeted therapy development. However, new approaches are being developed to leverage genetic information to predict patients' responses to treatment. These recent developments hold promise for early diagnosis, follow-up with personalised treatments with adjusted therapeutic doses, predictable responses, reduced adverse drug reactions, and personal health planning. The scenario is promising but calls for increased support for curiosity-driven research into the mechanisms of normal brain functioning as well as challenging adaptations of health care and research infrastructures, encompassing legal frameworks for analysing large amounts of personal data, a flexible regulatory framework for correlating big data analyses in cooperative networks between academia and the drug development industry, and finally new strategies for brain banking in order to increase access to brain tissue samples. To make personalised medicine for brain disorders a reality, a joint effort between all relevant stakeholders - among which patients and patient organisations should play an important role - is required.

Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3–96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders. ; The author list between I.A. and M.Z. is in alphabetic order. The authors were funded by the Research Council of Norway (276082 LifespanHealth (T.K.), 213837 (O.A.A), 223273 NORMENT (O.A.A.), 204966 (L.T.W.), 229129 (O.A.A.), 249795 (L.T.W.), 273345 (L.T.W.) and 283798 SYNSCHIZ (O.A.A.)), the South-Eastern Norway Regional Health Authority (2013-123 (O.A.A.), 2014-097 (L.T.W.), 2015-073 (L.T.W.) and 2016083 (L.T.W.)), Stiftelsen Kristian Gerhard Jebsen (SKGJ-MED-008), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC Starting Grant, Grant agreement No. 802998 BRAINMINT (L.T.W.)), NVIDIA Corporation GPU Grant (T.K.), and the European Commission 7th Framework Programme (602450, IMAGEMEND (A.M.-L.)). ; acceptedVersion

"For much of the twentieth century, philosophy and science went their separate ways. In moral philosophy, fear of the so-called naturalistic fallacy kept moral philosophers from incorporating developments in biology and psychology. Since the 1990s, however, many philosophers have drawn on recent advances in cognitive psychology, brain science, and evolutionary psychology to inform their work. This collaborative trend is especially strong in moral philosophy, and these three volumes bring together some of the most innovative work by both philosophers and psychologists in this emerging interdisciplinary field. The neuroscience of morality is in its infancy, with the first brain imaging studies of moral development undertaken only in 2001. The contributors to volume 3 sample the best work in this very new field, discussing a variety of approaches, including functional imaging, lesion studies, abnormal psychology, and developmental neuroscience. Each chapter includes an essay, comments on the essay by other scholars, and a reply by the author(s) of the original essay. Topics include the neural basis of moral emotions and moral judgments as well as comparisons of normal adult moral judgments with those made by children, adolescents, and people with psychopathy, brain damage, and autism"--Publisher's website.

AbstractProtein kinase B (PKB/AKT) is a central kinase involved in many neurobiological processes. AKT is expressed in the brain as three isoforms, AKT1, AKT2, and AKT3. Previous studies suggest isoform-specific roles in neural function, but very few studies have examined AKT isoform expression at the cellular level. In this study, we use a combination of histology, immunostaining, and genetics to characterize cell-type-specific expression of AKT isoforms in human and mouse brains. In mice, we find that AKT1 is the most broadly expressed isoform, with expression in excitatory neurons and the sole detectable AKT isoform in gamma-aminobutyric acid ergic interneurons and microglia. By contrast, we find that AKT2 is the sole isoform expressed in astroglia and is not detected in other neural cell types. We find that AKT3 is expressed in excitatory neurons with AKT1 but shows greater expression levels in dendritic compartments than AKT1. We extend our analysis to human brain tissues and find similar results. Using genetic deletion approaches, we also find that the cellular determinants restricting AKT isoform expression to specific cell types remain intact under Akt deficiency conditions. Because AKT signaling is linked to numerous neurological disorders, a greater understanding of cell-specific isoform expression could improve treatment strategies involving AKT.

Abstract
The boundaries between waking and sleeping—when falling asleep (hypnagogic) or waking up (hypnopompic)—can be challenging for our ability to monitor and interpret reality. Without proper understanding, bizarre but relatively normal hypnagogic/hypnopompic experiences can be misinterpreted as psychotic hallucinations (occurring, by definition, in the fully awake state), potentially leading to stigma and misdiagnosis in clinical contexts and to misconception and bias in research contexts. This Perspective proposes that conceptual and practical understanding for differentiating hallucinations from hypnagogic/hypnopompic experiences may be offered by lucid dreaming, the state in which one is aware of dreaming while sleeping. I first introduce a possible systematization of the phenomenological range of hypnagogic/hypnopompic experiences that can occur in the transition from awake to REM dreaming (including hypnagogic perceptions, transition symptoms, sleep paralysis, false awakenings, and out-of-body experiences). I then outline how metacognitive strategies used by lucid dreamers to gain/confirm oneiric lucidity could be tested for better differentiating hypnagogic/hypnopompic experiences from hallucinations. The relevance of hypnagogic/hypnopompic experiences and lucid dreaming is analyzed for schizophrenia and narcolepsy, and discussed for neurodegenerative diseases, particularly Lewy-body disorders (i.e. Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies), offering testable hypotheses for empirical investigation. Finally, emotionally positive lucid dreams triggered or enhanced by training/induction strategies or by a pathological process may have intrinsic therapeutic value if properly recognized and guided. The overall intention is to raise awareness and foster further research about the possible diagnostic, prognostic, and therapeutic implications of hypnagogic/hypnopompic experiences and lucid dreaming for brain disorders.

Neurological, Psychiatric, and Developmental Disorders -- Copyright -- REVIEWERS -- Preface -- Acknowledgments -- Contents -- Part I -- Executive Summary -- BACKGROUND -- SCOPE -- MAGNITUDE OF THE PROBLEM -- FINDINGS AND FUTURE STRATEGIES -- To Reduce the Burden of Brain Disorders Now -- To Create Options for the Future -- CONCLUSION -- 1 Introduction -- NEUROLOGICAL, PSYCHIATRIC, AND DEVELOPMENTAL DISORDERS -- CHALLENGES FOR THE CARE OF BRAIN DISORDERS -- GOALS OF THE STUDY -- STUDY APPROACH -- ORGANIZATION OF THE REPORT -- REFERENCES -- 2 The Magnitude of the Problem -- EFFECTS ON COMMUNITIES AND NATIONS -- The Disease Burden -- EFFECTS ON INDIVIDUALS AND FAMILIES -- Lost Productivity -- Stigma and Discrimination -- THE ROLES OF POVERTY AND GENDER INEQUALITY -- The Role of Poverty -- Poverty-Associated Risk Factors for Brain Disorders -- Unsafe and Unhygienic Living Conditions -- Hunger and Malnutrition -- Inadequate Access to Health Care -- Lack of Educational and Employment Opportunities -- The Role of Gender Inequality -- Postnatal Depression -- Rape and Sexual Violence -- HIV/AIDS -- Domestic Violence -- CAPACITY TO ADDRESS BRAIN DISORDERS -- REFERENCES -- 3 Integrating Care of Brain Disorders into Health Care Systems -- THE ROLE OF PRIMARY CARE IN ADDRESSING BRAIN DISORDERS -- DEVELOPING A SYSTEM OF CARE -- Primary Care -- The Role of Secondary and Tertiary Care -- BUILDING CAPACITY THROUGH TRAINING -- COLLABORATION WITH OTHER HEALTH AND NONHEALTH SECTORS -- Private Physicians -- Schools and Educators -- Community-Based Rehabilitation Programs -- Community Organizations -- Traditional Healers -- THE COST OF INTEGRATING SERVICES -- BUILDING RESEARCH CAPACITY THROUGH COLLABORATION -- POLICY IMPLICATIONS -- National Policy -- Local Policy -- INTERNATIONAL SUPPORT FOR SYSTEMS OF PRIMARY CARE.

Background: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people. Aims: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country. Methods: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27 + Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010. Results: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US. Discussion: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges. Recommendations: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.

Neuroprotection is a novel perspective for the treatment of disorders that lead to neurodegeneration and disabilities as a result of deterioration of neurons due to apoptosis, oxidative stress, excitotoxicity, and other mechanisms. These mechanisms have implications not only for neurodegenerative disorders, but also for schizophrenia, mood and cognitive disorders. The purpose of this book is to provide an up-to-date overview of basic and clinical studies concerning the neuroprotective approach, mechanisms, and several compounds with neuroprotective properties that may contribute to more effica.

AbstractNormal brain development involves a series of exquisitely complex and highly orchestrated events; disruptions in normal brain development provide a useful model for understanding infantile autism and other pervasive developmental disorders.

This chapter reviews family systems and developmental psychopathology, noting some aspects of the political /policy/practice context about the role of families in the development of psychopathology. To provide a focused account of family systems theory, it illustrates examples drawn primarily from the United States. After a brief historical look at how these theories have changed over time, the chapter illustrates how family systems and family risk factors approaches can be applied to the understanding of developmental psychopathology. It examines how family processes are implicated in explaining what happens when nonclinical families go through major life transitions, both expected and unexpected. The chapter then shows how formulations from a family systems or family risk factor perspective can provide value-added information, both in predicting the trajectories people follow in their journeys toward or away from diagnosed disorders, and in planning interventions for those at risk or distressed.

Aims: To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU. Method: Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY). Results: Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8 million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165 m vs. 2005: 82 m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (> 4%), ADHD (5%) in the young, and dementia (1–30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave, early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment. Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke. Conclusion: In every year over a third of the total EU population suffers from mental disorders. The true size of "disorders of the brain" including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs. We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century.